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Objective: To reveal differences in error pattern of phonemes and articulation between children using cochlear implants (CIs) and those using hearing aids (HAs) due to prelingual hearing disorder and help the education of children with prelingual hearing loss., Method: Children with prelingual hearing loss who were receiving auditory-verbal preschool education at an auditory center for hearing-impaired children (Fujimidai Auditory Center, Tokyo, Japan) from 2010 to 2020 were analyzed retrospectively. All participants underwent pure tone audiometry and monosyllabic intelligibility tests. The error answers were categorized into five patterns which was characterized by the substitution, addition, omission, failure, and no response according to consonant errors. In addition, the consonant errors classified into the manner of articulation and the differences of error patterns were analyzed between the HA and the CI group descriptively., Results: A total of 43 children with bilateral HAs and 46 children with bimodal CIs or bilateral CIs were enrolled. No significant between-group differences in median phoneme intelligibility were found. The most common error pattern was substitution in both HA and CI groups. The error number of addition pattern in the HA group was smaller than in the CI group. In both groups, the most common errors of articulation were flap errors, and the most common error patterns were flaps to nasals, nasals to nasals, plosives to plosives. In the HA group, plosives and nasals tended not to be recognized and in the CI group plosives were prone to be added to vowels., Conclusions: There were some different error patterns of articulation and consonant substitution between groups. Clarifying differences of phoneme that are difficult to hear and tend to be misheard would help for creating an effective approach to auditory training for children with hearing loss., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Objective The Patterns of Non-adherence to Anti-platelet Regimen in Stented Patients (PARIS) and Coronary Revascularization Demonstrating Outcome Study in Kyoto (CREDO-Kyoto) thrombotic and bleeding risk scores were established to predict ischemic and bleeding events in patients undergoing percutaneous coronary intervention (PCI). However, whether or not the combination of these risk scores is predictive of clinical outcomes is unclear. Methods This bicenter registry included a total of 1,098 patients with acute myocardial infarction (MI) undergoing primary PCI. Patients were divided into three groups according to the PARIS and CREDO-Kyoto thrombotic and bleeding risk scores. The study endpoints included the rates of both ischemic (cardiovascular death, recurrent MI, and ischemic stroke) and major bleeding (Bleeding Academic Research Consortium type 3 or 5) events at two years. Results Two years after primary PCI, ischemic and major bleeding events occurred in 17.3% and 10.2% of patients, respectively. The higher-risk categories of PARIS and CREDO-Kyoto scores were associated with increased risks of ischemic and bleeding events. The rates of ischemic and major bleeding events progressively increased with the increase in risk categories in the two risk scoring systems. In the receiver operating characteristic curve analysis, the addition of CREDO-Kyoto thrombotic and bleeding risk scores to PARIS scores significantly improved diagnostic ability in predicting ischemic (area under the curve: 0.59 vs. 0.63, p=0.01) and bleeding (area under the curve: 0.65 vs. 0.68, p=0.01) events. Conclusion The combinations of the PARIS and CREDO-Kyoto risk scores might be useful for evaluating ischemic and bleeding risks in patients with acute MI undergoing primary PCI.

Reducing casein kinase 1α (CK1α) expression inhibits the growth of multiple cancer cell lines, making it a potential therapeutic target for cancer. Herein, we evaluated the antitumor activity of FPFT-2216-a novel low molecular weight compound-in lymphoid tumors and elucidated its molecular mechanism of action. In addition, we determined whether targeting CK1α with FPFT-2216 is useful for treating hematopoietic malignancies. FPFT-2216 strongly degraded CK1α and IKAROS family zinc finger 1/3 (IKZF1/3) via proteasomal degradation. FPFT-2216 exhibited stronger inhibitory effects on human lymphoma cell proliferation than known thalidomide derivatives and induced upregulation of p53 and its transcriptional targets, namely, p21 and MDM2. Combining FPFT-2216 with an MDM2 inhibitor exhibited synergistic antiproliferative activity and induced rapid tumor regression in immunodeficient mice subcutaneously transplanted with a human lymphoma cell line. Nearly all tumors in mice disappeared after 10 days; this was continuously observed in 5 of 7 mice up to 24 days after the final FPFT-2216 administration. FPFT-2216 also enhanced the antitumor activity of rituximab and showed antitumor activity in a patient-derived diffuse large B-cell lymphoma xenograft model. Furthermore, FPFT-2216 decreased the activity of the CARD11/BCL10/MALT1 (CBM) complex and inhibited IκBα and NFκB phosphorylation. These effects were mediated through CK1α degradation and were stronger than those of known IKZF1/3 degraders. In conclusion, FPFT-2216 inhibits tumor growth by activating the p53 signaling pathway and inhibiting the CBM complex/NFκB pathway via CK1α degradation. Therefore, FPFT-2216 may represent an effective therapeutic agent for hematopoietic malignancies, such as lymphoma., Significance: We found potential vulnerability to CK1α degradation in certain lymphoma cells refractory to IKZF1/3 degraders. Targeting CK1α with FPFT-2216 could inhibit the growth of these cells by activating p53 signaling. Our study demonstrates the potential therapeutic application of CK1α degraders, such as FPFT-2216, for treating lymphoma., (© 2024 The Authors; Published by the American Association for Cancer Research.)

Background: Simple, noninvasive, and repeatable screening methods are essential for assessing swallowing disorders. We focused on patients with acute stroke and aimed to assess the characteristics of swallowing screening tests, including the modified Mann Assessment of Swallowing Ability score, tongue pressure, and repetitive saliva swallowing test (RSST), compared with detailed videofluoroscopic swallowing study (VFSS) findings to contribute as a helpful resource for their comprehensive and complementary use., Methods and Results: We enrolled first-ever patients with acute stroke conducting simultaneous assessments, including VFSS, modified Mann Assessment of Swallowing Ability score, tongue pressure measurement, and RSST. VFSS assessed aspiration, laryngeal penetration, oral cavity residue, vallecular residue, pharyngeal residue, and swallowing reflex delay. Screening tests were compared with VFSS findings, and multiple logistic analysis determined variable importance. Cutoff values for each abnormal VFSS finding were assessed using receiver operating characteristic analyses. We evaluated 346 patients (70.5±12.6 years of age, 143 women). The modified Mann Assessment of Swallowing Ability score was significantly associated with all findings except aspiration. Tongue pressure was significantly associated with oral cavity and pharyngeal residue. The RSST was significantly associated with all findings except oral cavity residue. Receiver operating characteristic analyses revealed that the minimum cutoff value for all VFSS abnormal findings was RSST ≤2., Conclusions: The modified Mann Assessment of Swallowing Ability is useful for broadly detecting swallowing disorders but may miss mild issues and aspiration. The RSST, with a score of ≤2, is valuable for indicating abnormal VFSS findings. Tongue pressure, especially in oral and pharyngeal residues, is useful. Combining these tests might enhance accuracy of the swallowing evaluation.

In recent years, hydrogen energy has garnered attention as a potential solution for mitigating greenhouse gas emissions. However, concerns regarding the inherent risk of hydrogen gas leakage and potential explosions have necessitated the development of advanced sensors. Within our research group, we have innovated an ultrathin platinum (Pt) film hydrogen sensor that gauges resistance changes in Pt thin films when exposed to hydrogen gas. Notably, the sensitivity of each sensor is contingent upon the thickness of the Pt film. To address the challenge of detecting hydrogen using multiple sensors, we integrated the ultrathin Pt film as a resistance element within a twin-T type notch filter. This filter exhibits a distinctive reduction in output signals at a specific frequency. The frequency properties of the notch filter dynamically alter with changes in the resistance of the Pt film induced by hydrogen exposure. Consequently, the ultrathin Pt film hydrogen sensor monitors output signal variations around the notch frequency, responding to shifts in frequency properties. This innovative approach enables the electrical control of sensor sensitivity by adjusting the operating frequency in proximity to the notch frequency. Additionally, the simultaneous detection of hydrogen by multiple sensors was successfully achieved by interconnecting sensors with distinct notch frequencies in series.

The Japanese version of high bleeding risk (J-HBR) criteria was domestically proposed to identify patients at HBR after percutaneous coronary intervention (PCI). The applicability of J-HBR on bleeding events has been validated, while whether J-HBR predicts ischemic events is uncertain. This bi-center registry included 904 patients with acute myocardial infarction (MI) undergoing primary PCI. Patients were stratified by the J-HBR major (1 point) and minor (0.5 point) criteria. Patients with J-HBR ≥ 1 point were diagnosed as having HBR. The primary endpoint was major adverse cardiovascular events (MACE), a composite of cardiovascular death, recurrent MI, and ischemic stroke, after discharge. Of the 904 patients, 451 (49.9%) had the J-HBR. The primary endpoint more frequently occurred in patients with J-HBR than in those without (10.9% vs. 4.9%, p < 0.001) during the median follow-up period of 522 days. Probability of MACE was progressively increased with the increase in the number of J-HBR major and minor criteria, in which severe anemia, severe chronic kidney disease, prior heart failure, peripheral artery disease, and prior ischemic stroke were identified as significant factors associated with MACE. In patients with acute MI undergoing PCI, the J-HBR criteria were predictive for ischemic outcomes after discharge, suggesting that the J-HBR criteria may be useful to identify patients at high bleeding and ischemic risks., (© 2023. Springer Nature Japan KK, part of Springer Nature.)

Aims: Several scoring systems, including the ABCD-GENE and HHD-GENE scores incorporating clinical and genetic factors, have been developed to identify patients likely to have high platelet reactivity on P2Y12 inhibitors, leading to increased risks of ischemic events. However, genetic testing is not widely available in daily practice. We aimed to evaluate the differential impact of clinical factors in the scores on ischemic outcomes in patients treated with clopidogrel and prasugrel., Methods: This bi-center registry included 789 patients with acute myocardial infarction (MI) undergoing percutaneous coronary intervention and treated with either clopidogrel or prasugrel at discharge. The relations of the number of clinical factors included in the ABCD-GENE (age ≥ 75 years, body mass index ＞30 kg/m 2 , chronic kidney disease, and diabetes) and HHD-GENE (hypertension, hemodialysis, and diabetes) scores to the primary endpoint of major cardiovascular events after discharge, a composite of death, recurrent MI, and ischemic stroke, were evaluated., Results: The number of clinical factors in the ABCD-GENE score was not predictive of ischemic outcomes after discharge in patients treated with clopidogrel and/or prasugrel, while the increase in the number of clinical factors of the HHD-GENE score was associated with an increased risk of the primary endpoint in a stepwise manner in patients on a P2Y12 inhibitor., Conclusions: Clinical factors listed in the HHD-GENE score may help stratify ischemic risks in patients with acute MI treated with clopidogrel and prasugrel, whereas risk stratification without genetic testing in patients treated with clopidogrel may be challenging.

Matrix metalloproteinase-7 (MMP-7) has been shown to play important roles in pathophysiological processes involved in the development/progression of diseases such as cancer and fibrosis. We discovered selective MMP-7 inhibitors composed of arylsulfonamide, carboxylate, and short peptides by a molecular hybridization approach. These compounds interacted with MMP-7 via multiple hydrogen bonds in the cocrystal structures. To obtain compounds for in vivo evaluation, we attempted structural optimization, particularly targeting Tyr167 at the S3 subsite through structure-based drug design, and identified compound 15 as showing improved MMP-7 potency and MMP subtype selectivity. A novel π-π stacking interaction with Tyr167 was achieved when 4-pyridylalanine was introduced as the P3 residue. Compound 15 suppressed the progression of kidney fibrosis in a dose-dependent manner in a mouse model of unilateral ureteral obstruction. Thus, we demonstrated, for the first time, that potent and selective MMP-7 inhibitors could prevent the progression of kidney fibrosis.

Aim: Wall shear stress (WSS) is the frictional force caused by viscous blood flowing along the vessel wall. Decreased WSS is associated with local vascular endothelial dysfunction and atherosclerosis. The vector flow mapping (VFM) technique detects the direction of intracardiac blood flow and WSS on the vessel wall with echocardiography. In this study, we examined carotid WSS by applying the VFM technique to the carotid arteries and evaluated its relationship with cerebral small vessel disease (SVD)., Methods: This is a single-center, prospective, observational study. We investigated the association between carotid WSS and SVD imaging, and cognitive outcomes in consecutive 113 patients with acute lacunar infarction., Results: Carotid WSS was negatively associated with age (r=-0.376, p＜0.001). Lower WSS was correlated with total SVD scores (ρ=-0.304, p=0.004), especially with enlarged perivascular space (EPVS) in the basal ganglia ＞10 (p＜0.001). The carotid intima-media thickness was not associated with the total SVD score (ρ=-0.183, p=0.052). Moreover, lower WSS was associated with executive dysfunction., Conclusion: EPVS has recently been reported as a marker of early SVD imaging, and executive dysfunction is common in vascular cognitive impairment. These results suggested that decreased carotid WSS based on vascular VFM, which can be measured easily, is associated with imaging and cognitive changes in the early stages of SVD.

Background: Chronic systemic inflammatory diseases (CSIDs) such as rheumatoid arthritis (RA) are reportedly associated with an increased risk of ischemic cardiovascular events including acute myocardial infarction (MI). However, data are limited on clinical characteristics and ischemic and bleeding outcomes after acute MI in patients with CSIDs., Methods: This bi-center registry included a total of 1001 patients with acute MI undergoing percutaneous coronary intervention. CSIDs included inflammatory rheumatological conditions (RA, systemic lupus erythematosus, vasculitis, etc.) and organ-specific diseases (chronic hepatitis, psoriasis, inflammatory bowel disease, etc.). The primary endpoint was net adverse clinical events (NACE), a composite of ischemic (all-cause death, MI, and ischemic stroke) and major bleeding (Bleeding Academic Research Consortium type 3 or 5) events, during hospitalization and after discharge., Results: Of the 1001 patients, 58 (5.8%) had CSIDs. The proportion of women was higher in patients with CSIDs than those without (37.9% vs. 22.1%, p = 0.009). During the hospitalization, no significant differences in the primary endpoint of NACE were observed between patients with and without CSIDs (10.3% vs. 12.7%, p = 0.84). During the median follow-up of 42.6 months after discharge, patients with CSIDs had a higher risk of NACE (22.5% vs. 10.1%, p = 0.01) than those without, mainly driven by an increased risk of ischemic events (18.4% vs. 8.4%, p = 0.03)., Conclusions: A small but significant proportion of patients with acute MI (5.8%) had CSIDs. While the incidence of in-hospital events was similar, patients with CSIDs had worse outcomes after discharge, suggesting that further clinical investigations and therapeutic approaches are needed in this patient subset., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Yaginuma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: Few studies have evaluated the mechanism of serious injury in acute hospitalization. Thus, the association between fall-related serious injury and activity during falls in acute care hospital remains unclear. Herein, we investigated the relationship between serious injury caused by fall and activity at the time of the fall in an acute care hospital., Methods: This retrospective cohort study was conducted at Asa Citizens Hospital. All inpatients aged 65 years and older were eligible for the study, which was conducted from April 1, 2021, through March 31, 2022. The magnitude of the association between injury severity and activity during the fall was quantified using odds ratio., Results: Among the 318 patients with reported falls, 268 (84.3%) had no related injury, 40 (12.6%) experienced minor injury, 3 (0.9%) experienced moderate injury, 7 (2.2%) experienced major injury. Moderate or major injuries caused by a fall was associated with the activity during the fall (odds ratio: 5.20; confidence intervals: 1.43-18.9, p = 0.013)., Conclusion: This study recognizes that falling during ambulation caused moderate or major injuries in an acute care hospital. Our study suggests that falls while ambulating in an acute care hospital were associated not only with fractures, but also with lacerations requiring sutures and brain injuries. Among the patients with moderate or major injuries, more falls occurred outside the patient's bedroom as compared with patients with minor or no injuries. Therefore, it is important to prevent moderate or major injuries related to falls that occur while the patient is walking outside their bedroom in an acute care hospital., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Kobayashi et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Bacillus Calmette-Guérin (BCG) remains the only approved tuberculosis (TB) vaccine despite limited efficacy. Preclinical studies of next-generation TB vaccines typically use a murine aerosol model with a supraphysiologic challenge dose. Here, we show that the protective efficacy of a live attenuated Mycobacterium tuberculosis (Mtb) vaccine ΔLprG markedly exceeds that of BCG in a low-dose murine aerosol challenge model. BCG reduced bacterial loads but did not prevent establishment or dissemination of infection in this model. In contrast, ΔLprG prevented detectable infection in 61% of mice and resulted in anatomic containment of 100% breakthrough infections to a single lung. Protection was partially abrogated in a repeated low-dose challenge model, which showed serum IL-17A, IL-6, CXCL2, CCL2, IFN-γ, and CXCL1 as correlates of protection. These data demonstrate that ΔLprG provides increased protection compared to BCG, including reduced detectable infection and anatomic containment, in a low-dose murine challenge model., Competing Interests: A.J.M. and D.H.B. are co-inventors on a provisional vaccine patent PCT/US2020/059152 (Mycobacterial compositions and biomarkers for use in treatment and monitoring of therapeutic responsiveness)., (© 2023 The Authors.)

Objective Oral diseases, including periodontitis and stomatitis, are highly prevalent worldwide and reportedly associated with the development of cardiovascular disease. Given the high rate of stomatitis in individuals wearing dentures, denture users may be at high risk of poor cardiovascular outcomes. We therefore investigated whether or not the use of dentures is associated with a poor clinical outcome in patients with acute myocardial infarction (MI). Methods This two-center retrospective observational study was conducted between January 2012 and March 2020. A total of 1,046 patients with acute MI who underwent primary percutaneous coronary intervention were divided into two groups according to denture use status. The primary outcomes included ischemic events (cardiovascular death, recurrent MI, and ischemic stroke) and major bleeding (Bleeding Academic Research Consortium type 3 or 5). Results Of the 1,046 patients with acute MI, 387 (37.0%) used dentures. An older age and prior MI were associated with an increased likelihood of denture use. During the mean 660-day follow-up period, ischemic and major bleeding events occurred in 169 (16.2%) and 102 (9.8%) patients, respectively. Denture use was associated with an increased risk of ischemic events, whereas no significant intergroup differences were observed in major bleeding outcomes. The results were similar among patients ≥75 years old. Conclusion More than one-third of the patients with acute MI wore dentures. Our findings suggest that denture use is significantly associated with an increased risk of ischemic events but not bleeding outcomes after acute MI.

Background: In patients with acute myocardial infarction (AMI), elevated natriuretic peptide (NP) concentrations are reportedly associated with worse clinical outcomes. This study evaluated the prognostic value of NP concentrations and in-hospital heart failure (HF) events after AMI.Methods and Results: The present bicenter registry included 600 patients with AMI undergoing percutaneous coronary intervention. HF was evaluated at 3 different time points after AMI: on admission, during hospitalization, and at the short-term follow-up at 1 month. When HF was present at each time point, 1 point was assigned to the "HF time points" (HFTP) risk scoring system; possible total scores on this system ranged from 0 to 3. The primary endpoint was a composite of all-cause death and HF rehospitalization after discharge. Among the 600 patients who survived to discharge, the primary outcome occurred in 69 (11.5%) during a mean follow-up period of 488 days. HF on admission, during hospitalization, and at the short-term follow-up were all significantly associated with subsequent clinical outcomes. Higher scores on the HFTP scoring system were related to an increased risk of the primary endpoint. Multivariable analysis indicated scores of 2 and 3 were independently associated with outcome events in a stepwise manner., Conclusions: Among patients with AMI, HF evaluation at different time points was useful in stratifying risks of mortality and HF rehospitalization after discharge.

Objective: We aimed to evaluate the visual measurements of coronary artery calcium (CAC) on nonelectrocardiogram (ECG)-gated chest computed tomography (CT) using a simple scoring method that involves counting the number of CT slices containing CAC. Materials and Methods: We analyzed 163 participants who underwent both coronary and chest CT examinations at six centers within 3 months. Agatston scores were calculated on standard ECG-gated scans and classified as none (0), mild (1-99), moderate (100-400), or severe (>400). Next, chest CT images were reconstructed to standard 5.0 mm axial slices. Then, CAC on chest CT scans was measured using two methods: the Weston score (sum of the assigned score of each vessel, range: 0-12) and number of slices showing CAC (Ca-slice#). Results: When the Weston score and Ca-slice# were divided into four levels according to the optimal divisional levels corresponding to the Agatston score classes, good agreements with the 4-grade Agatston score were observed (kappa value=0.610 and 0.794, respectively). The sensitivity and specificity of Ca-slice# ≥9 to identify severe Agatston scores of >400 were 86% and 96%, respectively. Conclusion: The Ca-slice#, a simple scoring method using chest CT scans, was in good agreement with the ECG-gated Agatston score., Competing Interests: Disclosure StatementShinichiro Fujimoto received grants from HeartFlow Japan G. K., Canon Medical Systems Corporation, and FUJIFILM Corporation, Edwards LifeSciences Ltd. All other authors declare no competing interests., (© 2023 The Editorial Committee of Annals of Vascular Diseases.)

Aims: The Academic Research Consortium (ARC) has proposed international criteria to standardize the definition of high bleeding risk (HBR) in patients undergoing percutaneous coronary intervention (PCI). In this context, Japan has also established its own guidelines, that is, the Japanese version of HBR (J-HBR) criteria. However, the J-HBR criteria have not been fully validated, especially in patients with acute myocardial infarction (MI)., Methods: This bi-center registry included 1079 patients with acute MI undergoing primary PCI in a contemporary setting. Patient bleeding risks were evaluated using the ARC-HBR and J-HBR criteria. The primary endpoint was rates of major bleeding events (Bleeding Academic Research Consortium type 3 or 5) at 1 year., Results: Of the 1079 patients, 505 (46.8%) and 563 (52.2%) met the ARC-HBR and J-HBR criteria, respectively. Patients who met the J-HBR criteria were found to have a higher rate of major bleeding events at 1 year than those who did not (12.8% vs. 3.3%, p＜0.001). When patients were scored and stratified using the J-HBR major and minor criteria, risks of major bleedings were progressively increased with the increase in the number of J-HBR criteria. In the receiver operating characteristic curve analysis, the ARC-HBR and J-HBR significantly predicted subsequent major bleedings after PCI, with ARC-HBR having greater predictive ability than J-HBR., Conclusions: More than half of the patients with acute MI undergoing primary PCI in Japan met the J-HBR criteria. Although the J-HBR criteria successfully identified patients who were likely to develop major bleeding events after primary PCI, the superiority of J-HBR to ARC-HBR in predicting bleeding outcomes warrants further investigation.

Tuberculosis (TB) remains a leading cause of morbidity and mortality worldwide. To date, the mainstay of vaccination involves the use of Mycobacterium bovis bacillus Calmette-Guérin (BCG), a live-attenuated vaccine that confers protection against extrapulmonary disease in infants and children but not against lung disease. Thus, there is an urgent need for novel vaccines. Here, we show that a multicomponent acellular vaccine (TB-MAPS) induces robust antibody responses and long-lived systemic and tissue-resident memory Th1, Th17, and cytotoxic CD4 + and CD8 + T cells, and promotes trained innate immunity mediated by γδT and NKT cells in mice. When tested in a mouse aerosol infection model, TB-MAPS significantly reduced bacterial loads in the lungs and spleens to the same extent as BCG. When used in conjunction with BCG, TB-MAPS further enhanced BCG-mediated protection, especially in the lungs, further supporting this construct as a promising TB vaccine candidate. IMPORTANCE Tuberculosis (TB) remains a leading cause of morbidity and mortality worldwide. Here, we evaluate a novel vaccine which induces a broad immune response to Mycobacterium tuberculosis including robust antibody responses and long-lived systemic and tissue-resident memory Th1, Th17, and cytotoxic CD4 + and CD8 + T cells. When tested in a mouse aerosol infection model, this vaccine significantly reduced bacterial loads in the lungs and spleens to the same extent as BCG. When used in conjunction with BCG, TB-MAPS further enhanced BCG-mediated protection, especially in the lungs, further supporting this construct as a promising TB vaccine candidate.

Wrong dose, a common prescription error, can cause serious patient harm, especially in the case of high-risk drugs like oral corticosteroids. This study aims to build a machine learning model to predict dose-related prescription modifications for oral prednisolone tablets (i.e., highly imbalanced data with very few positive cases). Prescription data were obtained from the electronic medical records at a single institute. Cluster analysis classified the clinical departments into six clusters with similar patterns of prednisolone prescription. Two patterns of training datasets were created with/without preprocessing by the SMOTE method. Five ML models (SVM, KNN, GB, RF, and BRF) and logistic regression (LR) models were constructed by Python. The model was internally validated by five-fold stratified cross-validation and was validated with a 30% holdout test dataset. Eighty-two thousand five hundred fifty-three prescribing data for prednisolone tablets containing 135 dose-corrected positive cases were obtained. In the original dataset (without SMOTE), only the BRF model showed a good performance (in test dataset, ROC-AUC:0.917, recall: 0.951). In the training dataset preprocessed by SMOTE, performance was improved on all models. The highest performance models with SMOTE were SVM (in test dataset, ROC-AUC: 0.820, recall: 0.659) and BRF (ROC-AUC: 0.814, recall: 0.634). Although the prescribing data for dose-related collection are highly imbalanced, various techniques such as the following have allowed us to build high-performance prediction models: data preprocessing by SMOTE, stratified cross-validation, and BRF classifier corresponding to imbalanced data. ML is useful in complicated dose audits such as oral prednisolone., Supplementary Information: The online version contains supplementary material available at 10.1007/s41666-023-00128-3., Competing Interests: Competing InterestsThe authors declare no competing interests., (© The Author(s) 2023.)

5-Diethylboryl-2,3'-bipyridine (1), which is inaccessible by conventional batch methods, was synthesized by using a flow microreactor. Compound 1 was obtained as an equilibrium mixture of a cyclic trimer and a cyclic tetramer in solution, the latter of which was crystallized in benzene by vapor diffusion of hexane at 7 °C. The dynamic nature of this system was confirmed by solvent- and concentration-dependent experiments. Notably, the dynamics was verified by using flow NMR spectroscopy, which revealed that the time required to reach equilibrium was influenced by the solvent ratio (<18 s, 24-28 s, and 34-42 s in 2 : 1, 1 : 1, and 1 : 2 mixtures of [D 6 ]acetone and C 6 D 6 , respectively). Compound 1 and 3-[4'-(diethylboryl)phenyl]pyridine (2) exhibited different self-assembly behavior in solution and crystals. Density functional theory calculations suggested that this difference was largely due to enhanced planarity between two consecutive aromatic rings., (© 2022 Wiley-VCH GmbH.)

Purpose: Pneumonia is the leading cause of mortality and morbidity in aging populations. Major causes of pneumonia in older adults are swallowing dysfunction and decreased airway clearance capacity, including an impaired cough reflex. Maximal tongue pressure is useful for evaluating swallowing function, and peak expiratory flow indirectly reflects cough strength. However, it is unclear whether they can predict pneumonia development in older adults. In this study, we investigated whether tongue pressure and peak expiratory flow could predict pneumonia development in older adults., Methods: This two-center prospective observational study included older adults aged 65 years or older without respiratory disease or head and neck cancer. We enrolled 383 consenting participants, many of whom had a history of stroke, and followed them for 2 years. The association between time to pneumonia development and tongue pressure or peak expiratory flow at enrollment was examined in a Cox proportional hazards model., Results: The mean age of the participants was 77.1 ± 6.2 years, and 36.0% of them were women. The mean tongue pressure was 35.4 ± 10.5 kPa and median peak expiratory flow was 218 L/min at enrollment. Six patients developed pneumonia during the study period. A low peak expiratory flow at enrollment was significantly associated with pneumonia development in the multivariate Cox proportional hazards model, but this association was not observed for tongue pressure., Conclusion: Decreased peak expiratory flow may predict pneumonia development in older adults. Future studies should investigate interventions for peak expiratory flow improvement., (© 2023. The Author(s), under exclusive licence to European Geriatric Medicine Society.)

Objective: Image evaluation after stent-assisted coil embolization (SAC) for a cerebral aneurysm is difficult with conventional MRA or CTA because of metal artifacts. Pointwise encoding time reduction with radial acquisition (PETRA)-MRA is a noninvasive imaging examination that can reduce metal artifacts. This study aimed to examine whether PETRA-MRA can be used as a follow-up imaging after SAC., Methods: Twelve patients (eight women and four men; mean age, 66.9 ± 13.2 years) underwent SAC for unruptured aneurysms and were retrospectively evaluated using time-of-flight (TOF)- and PETRA-MRA data from the same follow-up session. Two neurosurgeons independently compared the aneurysm occlusion status and flow visualization score in the stented parent artery (4-point scale, where 4 points represented excellent visualization) between TOF- and PETRA-MRA images. If DSA was performed within 3 months before or after PETRA-MRA, the aneurysm assessment was compared between MRA and DSA. The interobserver agreement for each MRA was evaluated., Results: Nine of the 12 patients underwent DSA within 3 months before and after TOF- and PETRA-MRA. The aneurysm occlusion status on DSA was more consistent with PETRA-MRA (eight of nine cases) than with TOF-MRA (one of nine cases; P = 0.023). The median visualization score of the stented parent artery was significantly higher for PETRA-MRA (4 [interquartile range {IQR} 3-4]) than for TOF-MRA (1 [IQR 1-1], P = 0.003). The interobserver agreement for evaluation of the aneurysm occlusion status and visualization score of the parent artery for PETRA-MRA were excellent (κ = 0.98 and 0.93, respectively). In one case, PETRA-MRA was able to detect aneurysm recurrence, leading to subsequent retreatment., Conclusion: PETRA-MRA is a noninvasive examination that can be used to evaluate the occlusion status of aneurysms after SAC and visualize the stented parent artery. PETRA-MRA is useful for repeated follow-up examinations after SAC., Competing Interests: The authors have no conflicts of interest to declare., (©2023 The Japanese Society for Neuroendovascular Therapy.)

Aims: High platelet reactivity (HPR) has been associated with an increased risk of thrombotic events in patients undergoing percutaneous coronary intervention. HPR has been well examined in patients treated with clopidogrel; however, HPR on prasugrel is poorly investigated., Methods: Four prospective studies were pooled, in which platelet reactivity on prasugrel was measured using VerifyNow assay; genotyping of CYP2C19 was also performed. Factors associated with HPR on prasugrel were identified using multivariable analysis to develop a risk prediction model., Results: In total, 180 patients were examined in this study, of whom 51 (28%) had HPR on prasugrel. The multivariable analysis indicated that hypertension, diabetes, hemodialysis, and the number of CYP2C19 loss-of-function (LOF) alleles are significant factors for HPR on prasugrel. These four factors were then incorporated to develop the HHD-GENE score. The receiver operating characteristic curve analysis showed that the HHD-GENE score predicted HPR on prasugrel (area under the curve (AUC) 0.74, best cutoff value 5, p＜0.001). With the best cutoff value, patients with the HHD-GENE score ≥ 5 had a significantly increased risk of HPR on prasugrel than their counterpart (50% vs. 18%, p＜0.001)., Conclusions: The HHD-GENE score consisting of hypertension, diabetes, hemodialysis, and CYP2C19 LOF alleles may be useful in identifying patients on prasugrel who are at high risk for HPR. External validation is needed to define the clinical utility of this novel scoring system.

Among patients with acute myocardial infarction (MI) complicated by cardiogenic shock (CS), in-hospital mortality remains high. In the present study, we aimed to identify factors associated with clinical outcomes of acute MI patients with CS in a contemporary setting. A total of 1102 patients with acute MI undergoing primary percutaneous coronary intervention were included, among whom 196 (17.8%) were complicated by CS. The primary outcome was all-cause death during hospitalization, and factors associated with in-hospital mortality were explored in patients with acute MI and CS. Of the 196 patients with acute MI complicated by CS, 77 (39.3%) died during hospitalization. The rates of non-ST-segment elevation MI (NSTEMI) (33.8% vs. 19.3%, p = 0.02) and culprit lesion in the left main or left anterior descending coronary artery (68.8% vs. 47.9%, p = 0.004) were higher, while left ventricular ejection fraction (LVEF) was lower (24.4 ± 11.7% vs. 39.7 ± 13.8%, p < 0.001) in non-survivors than in survivors. Multivariable analysis identified NSTEMI presentation and lower LVEF as independent predictors of in-hospital death. In conclusion, NSTEMI and low LVEF were identified as factors associated with higher in-hospital mortality. The identification of even higher-risk subsets and targeted therapeutic strategies may be warranted to improve survival of patients with acute MI and CS., Competing Interests: The authors declare no conflict of interest.

Introduction: The clinical course of hemodialysis patients with COVID-19 still remains unclear., Methods: Thirty-four hemodialysis patients were retrospectively enrolled. Patients were divided according to disease severity, and clinical symptoms and laboratory data at admission were compared., Results: The serum C-reactive protein (CRP) level, d-dimer level, and white blood cell (WBC) count were significantly higher in the group with critical disease than in the group with mild to severe disease (p = 0.005, p = 0.039, and p = 0.045). The serum CRP level exceeded 10 mg/dl within 7 days of clinical onset in all the cases with critical disease., Conclusion: Hemodialysis patients with COVID-19 who have elevated serum CRP and d-dimer levels, and an elevated WBC count at admission and patients with serum CRP levels exceeding 10 mg/dl before day 7 after clinical onset should be carefully monitored for possible progression to critical disease., (© 2021 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.)

Background: Recently, the impact of the lack of standard modifiable risk factors, including hypertension, diabetes, dyslipidaemia, and current smoking, has been investigated in ST-segment elevation myocardial infarction (MI). The present study aimed to evaluate clinical characteristics and prognosis of the patients with no standard risk factors in acute MI., Methods: This bi-centre registry included 1,093 patients with acute MI undergoing percutaneous coronary intervention. The participants were divided into two groups: patients having at least one of the four standard risk factors and those having none of the risk factors. The study endpoints included major adverse cardiovascular events (MACE) (death, recurrent MI, and stroke) and major bleeding events during hospitalisation. Any MACE and major bleeding events after discharge were also evaluated as an exploratory analysis., Results: Of 1,093 patients, 64 (5.9%) had none of the four standard risk factors. The patients with no standard risk factors were likely to present with Killip class IV and cardiac arrest. The rate of in-hospital MACE was higher in patients with no risk factors than in their counterparts (25.0% vs 9.9%; p<0.001), whereas the incidence of in-hospital major bleeding was not significantly different between the two groups (9.4% vs 6.7%; p=0.44). Active cancer and autoimmune/inflammatory diseases were often found in patients with no standard risk factors. After discharge, no significant differences were observed in the risks of MACE and major bleeding events between the two groups., Conclusions: No standard modifiable risk factors were not uncommon and were associated with poor short-term outcomes in patients with acute MI., (Copyright © 2022 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Objective: Diffusion-weighted imaging hyperintensities are observed in intracerebral hemorrhage patients at times and might be associated with unfavorable functional outcomes. However, the suitable time to evaluate diffusion-weighted imaging hyperintensities to influence stroke outcome remains unclear. This study investigated the associations between acute and sub-acute diffusion-weighted imaging hyperintensities and functional outcomes among patients with acute intracerebral hemorrhage., Methods: Diffusion-weighted imaging hyperintensities were evaluated within 24 h (acute phase) and at 14 ± 5 days (sub-acute phase). An unfavorable functional outcome was a score of 5-6 on the modified Rankin Scale at 3 months., Results: Among 268 intracerebral hemorrhage patients, diffusion-weighted imaging hyperintensities in the acute phase were observed in 32 (11.9%). Among 227 patients who underwent a second magnetic resonance imaging in the sub-acute phase, diffusion-weighted imaging hyperintensities were observed in 57 (25.1%). Multivariable analysis revealed that the baseline intracerebral hemorrhage volume, history of stroke, and severe white matter lesions were associated with sub-acute diffusion-weighted imaging hyperintensities. The patients with unfavorable outcomes (n = 37) had a higher frequency of sub-acute diffusion-weighted imaging hyperintensities than those without (n = 190) (51.4% vs. 20.0%, P < 0.001); the frequencies of acute diffusion-weighted imaging hyperintensities were not significantly different between the groups (13.5% vs. 10.0%, P = 0.559). Sub-acute diffusion-weighted imaging hyperintensities were independently associated with unfavorable outcomes after adjusting for confounding factors (Odds Ratio, 3.35, 95% CI 1.20-9.35, P = 0.021)., Conclusion: The rate of sub-acute diffusion-weighted imaging hyperintensities was higher than acute diffusion-weighted imaging hyperintensities among acute intracerebral hemorrhage patients and likely to be associated with unfavorable outcomes., Competing Interests: Declaration of Competing Interest Dr. Maruyama received Grants-in-Aid for Scientific Research (20K07887) and research support from Eisai, Pfizer, Takeda Pharmaceutical, Otsuka Pharmaceutical, Nihon Pharmaceutical, Shionogi, Teijin Pharma, Fuji Film, Sumitomo Dainippon Pharma, Nihon Medi-Physics, Bayer, MSD, Daiichi Sankyo, Kyowa Hakko Kirin, Sanofi, Novartis, Kowa Pharmaceutical, Astellas Pharma, Tsumura, and Japan Blood Products Organization, which are unrelated to the submitted work. All other authors declare that they have no conflicts of interest. Role of Funding Sources., (Copyright © 2022 Elsevier Inc. All rights reserved.)

IL-17 plays important roles in host defense against Candida albicans at barrier surfaces and during invasive infection. However, the role of IL-17 in host defense after colonization of the epidermis, a main site of C. albicans infection, remains poorly understood. Using a murine model of epicutaneous candidiasis without skin abrasion, we found that skin inflammation triggered by epidermal C. albicans colonization was self-limiting with fungal clearance completed by day 7 after inoculation in wild-type mice or animals deficient in IL-17A or IL-17F. In contrast, marked neutrophilic inflammation in the epidermis and impaired fungal clearance were observed in mice lacking both IL-17A and IL-17F. Clearance of C. albicans was independent of Dectin-1, Dectin-2, CARD9 (caspase-recruitment domain family, member 9), TLR2 (Toll-like receptor 2) and MyD88 in the epidermal colonization model. We found that group 3 innate lymphoid cells (ILC3s) and γδT cells were the major IL-17 producers in the epicutaneous candidiasis model. Analyses of Rag2-/- mice and Rag2-/-Il2rg-/- mice revealed that production of IL-17A and IL-17F by ILC3s was sufficient for C. albicans clearance. Finally, we found that depletion of neutrophils impaired C. albicans clearance in the epidermal colonization model. Taken together, these findings indicate a critical and redundant function of IL-17A and IL-17F produced by ILC3s in host defense against C. albicans in the epidermis. The results also suggest that epidermal C. albicans clearance is independent of innate immune receptors or that these receptors act redundantly in fungal recognition and clearance., (Published by Oxford University Press on behalf of The Japanese Society for Immunology 2022.)

Taurine, a sulfur-containing β-amino acid, is present at high concentrations in mammalian tissues and plays an important role in several essential biological processes. However, the genetic mechanisms involved in these physiological processes associated with taurine remain unclear. In this study, we investigated the regulatory mechanism underlying the taurine-induced transcriptional enhancement of the thioredoxin-interacting protein (TXNIP). The results showed that taurine significantly increased the luciferase activity of the human TXNIP promoter. Further, deletion analysis of the TXNIP promoter showed that taurine induced luciferase activity only in the TXNIP promoter region (+200 to +218). Furthermore, by employing a bioinformatic analysis using the TRANSFAC database, we focused on Tst-1 and Ets-1 as candidates involved in taurine-induced transcription and found that the mutation in the Ets-1 sequence did not enhance transcriptional activity by taurine. Additionally, chromatin immunoprecipitation assays indicated that the binding of Ets-1 to the TXNIP promoter region was enhanced by taurine. Taurine also increased the levels of phosphorylated Ets-1, indicating activation of Ets-1 pathway by taurine. Moreover, an ERK cascade inhibitor significantly suppressed the taurine-induced increase in TXNIP mRNA levels and transcriptional enhancement of TXNIP. These results suggest that taurine enhances TXNIP expression by activating transcription factor Ets-1 via the ERK cascade.

Aim: High platelet reactivity (HPR) is associated with increased risks of thrombotic events in patients with coronary artery disease. The recently developed ABCD-GENE score identified five clinical and genetic factors (age, body mass index, chronic kidney disease, diabetes, and the CYP2C19 loss-of-function allele) for HPR, although the significance of various stages of each factor is unclear., Methods: Four prospective studies were pooled, in which platelet reactivity was measured using the VerifyNow assay with clopidogrel and prasugrel; genotyping of CYP2C19 was also performed. Each component of the ABCD-GENE score was divided into three subcategories. VerifyNow P2Y12 reactivity units ＞208 were defined as HPR., Results: A total of 184 patients were included, of which 111 (60%) and 51 (28%) had HPR with clopidogrel and prasugrel. Chronic kidney disease had an impact on HPR on both clopidogrel and prasugrel, whereas the impact of diabetes was more evident in patients treated with prasugrel. Although the number of CYP2C19 loss-of-function alleles was clearly associated with a likelihood of HPR with clopidogrel, P2Y12 reactivity units with prasugrel treatment were also significantly and progressively higher in patients with more CYP2C19 loss-of-function alleles., Conclusions: Clinical and genetic factors had a differential effect on a P2Y12 inhibitor reactivity with clopidogrel and prasugrel in patients with coronary artery disease. The severity of the factors also had a different impact on HPR.

Natural disasters are reported globally, and one source of severe damage to cities is flooding caused by locally heavy rain. Sharing of local weather information can save lives. However, it is difficult to collect local weather information in real-time because such data collection requires bulky, expensive sensors. For local, real-time monitoring of heavy rain and wind, a sensor system should be simple and low-cost so that it can be attached to a variety of surfaces, including roofs, vehicles, and umbrellas. To develop simple, low-cost multitasking sensors located on nonplanar surfaces, a flexible rain sensor to monitor waterdrop volume and wind velocity is devised. To monitor both simultaneously, a laser-induced graphene-based superhydrophobic conductive film is introduced. Using the superhydrophobic surface, water dynamics are measured when waterdrops collide with the sensor surface, and obtained time-series data are processed using "reservoir computing" to extract the volume and velocity from a single sensor as multitasking electronics. As a proof-of-concept, it is shown that the sensor measures continuous, long-term volume and wind-change dynamics. The results demonstrate feasibility of multitasking electronics with reservoir computing to reduce sensor integration complexity with low power consumption for both sensor and signal processing., (© 2022 Wiley-VCH GmbH.)

Background: In acute myocardial infarction (MI), the prognosis has been improved, and the length of hospital stay has been shortened. In the present study, we aimed to evaluate the potential of identifying low-risk patients for early discharge after acute MI using the GRACE and CADILLAC risk scores., Methods: This bi-center registry included 797 patients with acute MI undergoing primary percutaneous coronary intervention. Patients were divided into 3 groups according to the tertiles and pre-defined thresholds of the GRACE and CADILLAC scores. The primary endpoint was a composite of in-hospital major adverse events (all-cause death, sustained ventricular arrhythmia, recurrent MI, heart failure requiring intravenous treatment, stroke, and major bleeding events)., Results: Of 797 patients, 271 (34.0%) and 316 (39.7%) had low GRACE and CADILLAC risk scores. During the hospitalization, 251 (31.5%) patients had major adverse events. Higher GRACE and CADILLAC scores were associated with longer length of stay and higher in-hospital adverse event rates. In patients with low GRACE and/or CADILLAC risk scores, 16 (5.9%) and 16 (5.1%) had in-hospital adverse events, most of which occurred within 3 days. Only 1 (0.4% and 0.3%) patient had major adverse events on day 4 or later in the low GRACE and CADILLAC risk score groups., Conclusion: In patients with acute MI with low GRACE and/or CADILLAC risk scores who were free from acute events within 3 days, early discharge after primary percutaneous coronary intervention may be feasible and safe., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022. Published by Elsevier Ltd.)

Non-exchangeable K released from soil minerals can reduce radiocesium transfer to plants, as well as exchangeable K. We investigated the effect of non-exchangeable K on radiocesium transfer to soybean, and the non-exchangeable K extraction method most suitable for estimating the transfer risk. In Fukushima Prefecture, Japan, 106 soils were collected from 89 soybean fields during 2014-2018 to analyze non-exchangeable K contents using three methods: boiling nitric acid extraction, tetraphenyl‑boron extraction, and mild tetraphenyl‑boron extraction. The non-exchangeable K contents quantified by the former two methods were dependent on the amount of micas, which are K-bearing minerals. The non-exchangeable K content by mild tetraphenyl‑boron extraction depended on the amount of K fertilizer application and K-fixing minerals but not on micas, indicating that it reflects fertilizer K fixed by the minerals. The soil-to-plant transfer factor of radiocesium was most correlated with the non-exchangeable K content by the mild extraction (r s = -0.67). This correlation was also stronger than that between exchangeable K and the transfer factor (r s = -0.40). As non-exchangeable K content increased, the exchangeable radiocesium fraction decreased, indicating that radiocesium was fixed together with K. Additionally, multiple regression analysis indicated that non-exchangeable K by the mild extraction significantly decreased the transfer factor even if the exchangeable radiocesium fraction was kept constant. Thus, the fixed K was considered to repress radiocesium transfer to soybean through both radiocesium fixation and K supply. With the criterion of total extracted K, the sum of exchangeable and non-exchangeable K, as 65 mg K 2 O 100 g -1 by the mild extraction, fields with high and low transfer factors were able to be differentiated more effectively than with a current criterion of exchangeable K as 50 mg K 2 O 100 g -1 . The results revealed that mild tetraphenyl‑boron extraction is effective for estimating radiocesium transfer to soybean., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The PARIS and CREDO-Kyoto risk scores were developed to identify patients at risks of thrombotic and bleeding events individually after percutaneous coronary intervention (PCI). However, these scores have not been well validated in different cohorts.Methods and Results:This 2-center registry enrolled 905 patients with acute myocardial infarction (MI) undergoing primary PCI. Patients were divided into 3 groups according to the PARIS and CREDO-Kyoto thrombotic and bleeding risk scores. The study endpoints included ischemic (cardiovascular death, recurrent MI, and ischemic stroke) and major bleeding events. Of 905 patients, 230 (25%) and 219 (24%) had high thrombotic and bleeding risks, respectively, with the PARIS scores, compared with 78 (9%) and 50 (6%) patients, respectively, with the CREDO-Kyoto scores. According to the 2 scores, >50% of patients with high bleeding risk had concomitant high thrombotic risk. During the mean follow-up period of 714 days, 163 (18.0%) and 95 (10.5%) patients experienced ischemic and bleeding events, respectively. Both PARIS and CREDO-Kyoto scores were significantly associated with ischemic and bleeding events after primary PCI. For ischemic events, the CREDO-Kyoto rather than PARIS thrombotic risk score had better diagnostic ability., Conclusions: In the present Japanese cohort of acute MI patients undergoing contemporary primary PCI, the PARIS and CREDO-Kyoto thrombotic and bleeding risk scores were discriminative for predicting ischemic and bleeding events.

Low-cost PM 2.5 sensors are now used worldwide to assess air pollution. However, their operation is generally challenging in severely cold regions like Siberia, Alaska, the Arctic, and Antarctica. We made an insulation box with automatic internal temperature control developed for a low-cost PM 2.5 sensor to maintain a warm operational environment with four light-bulb heaters when the air temperature inside of the insulation box falls slightly below 5 °C under the current preset temperature setting. We confirmed the performance of the temperature controller with four light-bulb heaters in a -25 °C cold temperature room. In addition, we found that the insulation box must be attached to a small electric fan to forcibly ventilate the box to accurately reflect the external ambient air conditions into the insulating box. Our observations with the data from our low-cost PM 2.5 sensor fitted with the insulation box were validated against the Sapporo National Ambient Air Monitoring Station (NAAMS) data in Sapporo, Japan, showing good correspondence with the hourly station-measured data. Then, we installed our PM 2.5 measurement system on the roof of the International Arctic Research Center (IARC), University of Alaska Fairbanks, Alaska, USA, in June 2019. The sensor sufficiently captured two instances of significant increases in PM 2.5 mass concentrations during the Alaskan wildfires in the summer of 2019. Our developed insulation box for low-cost PM 2.5 sensors, called "the portable PM 2.5 measurement system for cold regions", will help assess air quality in many cold regions in future studies., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

V-shaped xanthene dyes capable of predicting absorption and emission wavelengths are described. These dyes were synthesized by bridging a xanthene ring and an aryl moiety of fluorescein through ether covalent bonds. These dyes showed longer absorption and emission wavelengths than those of the parent fluorescein. Furthermore, substituents introduced on the aryl moiety mainly affected the lowest unoccupied molecular orbital energy level of the molecule. Therefore, the Hammett substituent constants could be used to predict the absorption and emission wavelengths of the compound.

Atherosclerosis is an important risk factor for cognitive decline. This study aimed to investigate the relationship of ankle-brachial pressure index (ABI) and brachial-ankle pulse wave velocity (baPWV) with cognitive function in patients with lacunar infarction. We included records of consecutive patients with their first-ever acute stroke and a diagnosis of lacunar infarction through magnetic resonance imaging (MRI) from July 1, 2011 to December 31, 2018. We excluded patients diagnosed with dementia, including strategic single-infarct dementia, before or after stroke onset. Moreover, we excluded patients with one or more microbleeds, severe white matter lesions, or severe medial temporal atrophy on MRI. For ABI, we used the lower ankle side and divided the results into ABI < 1.0 and ABI ≥ 1.0. For baPWV, we used the higher ankle side and divided the results into two groups based on the median value of the participants. We analyzed 176 patients with stroke (age 72.5 ± 11.4 years, 67 females). The median score on the Mini-Mental State Examination (MMSE) was 27. The number of patients with ABI < 1.0 was 19 (10.8%). Univariate analysis revealed that the MMSE score was associated with age, body mass index, education, chronic kidney disease, periventricular hyperintensity, and ABI < 1.0 (p < 0.10), but not baPWV. Multivariate analysis revealed that body mass index (p = 0.039) and ABI < 1.0 (p = 0.015) were independently associated with the MMSE score. For patients with lacunar infarction, a lower ABI, but not a higher PWV, was associated with cognitive decline., Competing Interests: The authors have declared that no competing interests exist.

Objectives: Lateral medullary infarction mainly impairs the pharyngeal phase of swallowing. We aimed to investigate the utility of the assessment tools of swallowing function in patients with lateral medullary infarction and to determine the factors that could predict the outcomes of swallowing function., Materials and Methods: 15 patients with lateral medullary infarction who were admitted to Suiseikai Kajikawa Hospital between August 1, 2016, and March 31, 2020 (age 62.7 ± 14.8 years, 5 women) were enrolled in this prospective study. The diagnosis was made using brain magnetic resonance imaging. We analyzed the factors associated with severe swallowing dysfunction, which was defined as the necessity for tube feeding on the 90th day from admission, with multiple logistic regression analysis., Results: Multivariate analyses identified the repetitive saliva swallowing test, modified water swallowing test, and vertical spread of stroke lesions as independent significant factors affecting severe swallowing dysfunction (p = 0.002, 0.016, and 0.011, respectively). The sub-scores of the pharyngeal phase of the Mann Assessment of Swallowing Ability were also significantly associated with severe swallowing dysfunction (p < 0.001). However, tongue pressure, severe passage pattern abnormality on videofluoroscopic examination, and vertebral artery dissection were not significantly associated with swallowing dysfunction., Conclusions: Since lateral medullary infarction presents with swallowing dysfunction mainly in the pharyngeal phase, tools that can be used to evaluate the pharyngeal phase of swallowing, such as repetitive saliva swallowing test and modified water swallowing test, are moreuseful than tongue pressure measurement., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

This study aimed to develop a method to determine the degree of oocyte maturation in metaphase II in situ based on the balance between mitochondrial respiratory activity and lipid metabolism using resonance Raman spectroscopy. A decrease in the respiratory activity of overmatured oocytes was indicated by the reduced intensities of the resonance Raman bands corresponding to reduced cytochrome c in the cytoplasm. Moreover, the increased lipid concentration in overmature oocytes indicated lower lipid metabolism with a decreased mitochondrial function. New indexes were defined in terms of the ratios of the representative Raman peak intensities of reduced cytochrome c (750 and 1127 cm -1 ) to those of lipids (1438 cm -1 ) and they successfully classify the oocytes into groups based on their quality, which varied with their maturation degree. The high development rate of embryos that were fertilized in vitro after laser irradiation showed that laser irradiation was noninvasive to oocytes. The evaluation of two factors in situ , the active respiration and lipid metabolism, means to catch the most fundamental biochemical reactions of life activities. Our results demonstrate the potential application of resonance Raman spectroscopy as a new, noninvasive, and universal cell evaluation technology, for not only oocytes but also more general cells such as somatic cells and iPS cells.

Patients with cancer have an increased risk of cardiovascular events including myocardial infarction (MI) and vice versa, and are at high risks of ischemic and bleeding events after MI. However, short- and long-term clinical outcomes in patients with acute MI based on cancer status are not fully understood. This bi-center registry included 903 patients with acute MI undergoing primary percutaneous coronary intervention in a contemporary setting. Patients were divided into active cancer, a history of cancer, and no cancer according to the status of malignancy. Major adverse cardiovascular events (MACE), a composite of all-cause death, recurrent MI, and stroke, and major bleedings were evaluated. Of 903 patients, 49 (5.4%) and 65 (7.2%) had active cancer and a history of cancer, and 87 (9.6%) patients died during the hospitalization. In-hospital MACE was not significantly different among the 3 groups (16.3% vs 10.8% vs 10.9%, p = 0.48), whereas the rate of major bleeding events during the index hospitalization was significantly higher in patients with active cancer than their counterpart (20.4% vs 6.2% vs 5.8%, p = 0.002). After discharge, patients with active cancer had an increased risk of MACE and major bleedings compared with those with a history of cancer and no cancer during the mean follow-up period of 853 days. In conclusions, active cancer rather than a history of cancer and no cancer had significant impact on in-hospital bleeding events, and MACE and major bleedings after discharge in patients with acute MI undergoing primary percutaneous coronary intervention., Competing Interests: Disclosures The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aim: We evaluated the safety and potential clinical impact of shortened ramucirumab infusion in Japanese patients from clinical studies., Methods: Multivariate logistic regression analysis was used to assess any association between infusion rate and increased risk of an immediate infusion-related reaction(IRR). Population pharmacokinetic modeling was used to simulate concentration-time profiles and exposure parameters following a 30- or 60-minute infusion with ramucirumab., Results: From 8 pooled ramucirumab clinical studies, 55 of 559(9.8%)Japanese patients experienced at least one immediate IRR(any grade). When grouped according to infusion rate quartile, the incidence of immediate any-grade IRR was similar across quartiles. Infusion rate was not significantly associated with an increased risk of an immediate IRR; odds ratio per 1 mg/min increase was 0.912, 95% confidence interval 0.724 to 1.149, p=0.436. Patients aged ≥65 years may have a reduced risk of an immediate IRR compared with those aged <65 years, and premedication use was also associated with a reduced risk. Ramucirumab pharmacokinetic profiles were comparable following a 30- or 60-minute infusion., Conclusions: A shortened infusion duration of ramucirumab is unlikely to affect the efficacy or safety profile in Japanese patients and may be clinically beneficial for patients and health care providers., Clinical Trial Registration: RAINBOW-NCT01170663, RAISE- NCT01183780, REACH-NCT01140347, REACH-2-NCT02435433, RAINFALL-NCT02314117, RANGE-NCT02426125, RELAY-NCT02411448, I4T-MC-JVCG-NCT01703091.

Field and pot experiments were conducted to evaluate the effectiveness of coarse Finnish phlogopite application to reduce radiocesium uptake by paddy rice (Oryza sativa L.). The application of phlogopite was expected to reduce radiocesium uptake by crops through K supply and radiocesium retention. Three fields were set in Fukushima Prefecture, and coarse (mean particle size of 450 μm) phlogopite from Siilinjärvi (Finland) was applied at a rate of 5 t ha -1 . Paddy rice was cultivated for 2-4 successive years. In all fields, the average 137 Cs transfer factor (TF) of brown rice harvested from plots with added phlogopite was significantly lower than that of brown rice from plots without added phlogopite over the 2-4-year experiments. TF was decreased by up to 80% following phlogopite application, without an adverse effect on yield. Exchangeable K and soil solution K were higher in the soils with added phlogopite, suggesting K released from phlogopite reduced 137 Cs uptake by paddy rice. Moreover, in a pot cultivation experiment, even when 55% of the total K was removed from phlogopite prior to application, the TF in pots with phlogopite application was less than half of that in pots without added phlogopite. The results from the field study and the pot cultivation experiment suggested that the application of Finnish phlogopite is effective to reduce the TF of brown rice. Exchangeable K and tetraphenylborate-extractable-K (TPB-K) at rooting stage, and soil solution K at tillering and heading stages showed significant negative correlation with TF. TPB-K was significantly positively correlated with soil solution K at tillering stage and heading stage, whereas exchangeable K at rooting stage did not exhibit significant correlation with soil solution K at heading stage. The results suggest that TPB-K is more reliable than exchangeable K, which could facilitate as a basis of K fertilizer recommendation for radiocesium-contaminated fields., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Recent guidelines recommend risk stratification using objective scoring systems in patients with acute coronary syndrome. In this context, the CADILLAC (Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications) and GRACE (Global Registry of Acute Coronary Events) risk scores were both originally established to predict short-term mortality. However, their impact on short- and long-term clinical outcomes in a contemporary cohort of patients with acute myocardial infarction (MI) is unclear., Methods: This bi-center registry included 809 patients with acute MI undergoing primary percutaneous coronary intervention. Patients were divided into three groups according to the pre-defined thresholds and tertiles of the CADILLAC and GRACE scores. The study endpoints included all-cause death and major adverse cardiovascular events (MACE) during the index hospitalization and after discharge., Results: Of 809 patients, 323 (39.9%) and 255 (31.5%) had high CADILLAC and GRACE risk scores. During the index hospitalization, 61 (7.5%) patients died and 262 (32.4%) had MACE. Both CADILLAC and GRACE risk scores were associated with in-hospital mortality and MACE rates. After discharge, out of 683 patients with available follow-up information who survived to discharge, 42 (6.1%) died and 123 (18.0%) had MACE during the median follow-up period of 632 days. Significantly higher incidence of MACE in higher CADILLAC and GRACE risk scores was observed in a stepwise manner., Conclusion: Both CADILLAC and GRACE risk scores were predictive for short- and long-term mortality and MACE rates in a contemporary cohort of acute MI patients undergoing primary percutaneous coronary intervention., (Copyright © 2021. Published by Elsevier Ltd.)

Objectives: To reframe the criteria for pediatric cochlear implants (CIs) in Japan, we investigated monosyllabic and word speech perception at the time of school entry in deaf or hard of hearing (D/HH) children who underwent auditory-verbal therapy (AVT) with hearing aids (HAs) or CIs in early childhood., Methods: D/HH children who started AVT at Fujimidai Auditory Center for Hearing-Impaired Children before the age of 1 year and who underwent auditory assessment in the previous year of schooling (at the age of 5 or 6) from 2010 to 2020 were enrolled in this study. The results of hearing level tests with or without amplification and monosyllabic and word speech discrimination were assessed., Results: The children with profound hearing impairment (>90 dB HL) had worse speech perception than children with CIs. The children with severe hearing impairment (>70-90 dB HL) did not show any significant differences in speech perception compared with the children with CIs. The children with HAs with a wearing threshold <40 dB HL did not show any significant differences in speech perception from the children with CIs., Conclusion: D/HH children with audiologic thresholds greater than 90 dB HL or aided thresholds greater than 40 dB HL should be considered for CIs to ensure development of appropriate listening and spoken language., (Copyright © 2021 Elsevier B.V. All rights reserved.)